More than 500 subjects from 41 families with dominantly inherited facioscapulohumeral muscular dystrophy (FSHD) were studied at the Royal Hospital for Sick Children, St. Michael’s Hill, Bristol and the University of Wales College of Medicine, Heath Park, Cardiff, Wales. 168 subjects were affected and 330 were unaffected. Dominant inheritance was proven in 28 families and no evidence for recessive inheritance was found in the remainder. New mutation accounted for six isolated cases. The prevalence of FSHD in Wales was estimated at 2/100,000. Estimates of penetrance values were less than 5% at 0-4 years, 21% at 5-9 years, 58% at 10-14 years, 86% at 15-19 years and 95% at 20 years and over. Early onset is associated with the greatest chance of disability in later life. Proximal lower limb weakness was present in 39% aged less than 20 years, 46% aged 20-40 years, and 68% aged more than 40 years. Asymmetry of scapular and upper limb involvement was evident in 65% of 113 affected subjects. Creatine kinase is elevated in 80% of affected males under 40 year and 48% of affected women, but use of CK as a presymptomatic test for FSHD is limited. There was no clinical evidence of significant genetic heterogeneity between the 11 largest families studied. [1]

COMMENT. The genetic homogeneity for FSHD demonstrated in this study facilitates genetic counseling and answers to questions raised by family members. Different modes of presentation, particularly with respect to pelvic and peroneal involvement may be observed in various members of large kindreds. The recent assignment of the gene for FSHD to chromosome 4 will help to clarify some of the counseling issues, including families diagnosed as FSH type spinal muscular atrophy where the same genetic locus is involved. The risk of disability and wheelchair requirement in later life can be assessed by the reported age of onset and the occurrence of proximal lower limb weakness by age 20 years. The authors estimate that 19% of FSHD heteroxygotes will require a wheelchair by 40 years or over and 30% remain only mildly affected throughout life. Since asymmetry of weakness correlates with handedness, the overuse of limbs and particularly body building exercises should be discouraged.